Genome Study Points to New Culprit for Schizophrenia

FRIDAY Feb. 6, 2009 -- Large, rare structural changes in DNA called copy number variants may play a role in schizophrenia, according to U.S. researchers, who said their findings support a sharp change of direction in genetics research on schizophrenia.

Over the past two decades, researchers have identified dozens of genes and single nucleotide polymorphisms (SNPs or "snips") that could be linked to schizophrenia. But this new study dismisses all of them.

"The literature is replete with dozens of genes and SNPs identified as associated with schizophrenia. But we systematically retested all the leading candidates and concluded that most, if not all of them, are false positives," study lead author Anna Need, a postdoctoral associate at the Center for Human Genome Variation at the Duke Institute for Genome Sciences & Policy, said in a Duke University news release.

Most of the previous studies were too small to properly assess the role of SNPs in schizophrenia, Need said.

She and her colleagues analyzed the genomes of schizophrenia patients and healthy people for SNPs and copy number variants (CNVs). None of the previously identified SNPs appeared significant in schizophrenia, but the researchers identified several CNVs they believe may be associated with the psychiatric disorder.

CNVs are common and usually appear as deletions or duplications of significant stretches of DNA. But the largest deletions -- those over 2 million bases long -- appear only in people with schizophrenia, Need said.

The study was published Feb. 6 in the journal PLoS Genetics.

"What this means is that if we are going to make real headway in assessing genetic links to schizophrenia, we will have to sequence the entire genome of each schizophrenia patient," Need said. "That is a tremendous amount of work, but it is the only way we will be able to find these extremely rare variations."